A wide variety of bioactive peptides and peptide analogs have been used as active agents for the treatment of various conditions. These active agents are generally administered in connection with a polymeric delivery system to control the release of the agent. For example, peptide analogs of the natural hypothalamic hormone LHRH (Luteinizing Hormone Releasing Hormone, a decapeptide) are of therapeutic value when administered for a prolonged period of time with the appropriate delivery system. Commercially successful delivery systems include microspheres, microcapsules, microgranules and other implant forms which, when injected subcutaneously or intramuscularly, release the LHRH analog from a biocompatible and biodegradable matrix. The matrix is frequently a copolymer of lactic and glycolic acid ("PLGA", polylactic glycolic acid) as described, for example, in U.S. Pat. Nos. 3,773,919, 3,887,499, 4,675,189, 4,767,628 and many others.
It has been assumed that a continuous or monophasic release of such bioactive agents is a highly desirable feature of such formulations (see, e.g., U.S. Pat. No. 5,366,734). In fact, it has now been realized that what is really needed is to have the "therapeutic" effect of the peptide or peptide analog be maintained or sustained over a relatively long span of time (e.g., three to six months or longer). Thus, improvements in this area are desired and necessary.